Chronic myeloid leukemia stem cells and molecular target therapies for overcoming resistance and disease persistence

Int J Hematol. 2018 Oct;108(4):365-370. doi: 10.1007/s12185-018-2519-y. Epub 2018 Aug 28.

Abstract

Chronic myeloid leukemia (CML) is effectively treated with tyrosine kinase inhibitors (TKI) targeted against BCR-ABL. We previously reported the investigation of residual CML diseases during TKI treatment using FACS-sorting and quantitative RT-PCR of BCR-ABL among each population; total mononuclear cells, hematopoietic stem cells, and myeloid progenitors. The observations also implied that the second-generation of ABL-tyrosine kinase inhibitors (2nd TKIs), dasatinib or nilotinib therapy can be more promising approach for efficient reduction of the CML stem cells. Moreover, we need to develop the evaluation method of the residual CML diseases to establish rational therapy-cessation strategies in CML.

Keywords: BCR-ABL; Chronic myeloid leukemia; Leukemia stem cells; Tyrosine kinase inhibitors.

Publication types

  • Review

MeSH terms

  • Dasatinib / therapeutic use*
  • Drug Resistance, Neoplasm / drug effects*
  • Fusion Proteins, bcr-abl* / antagonists & inhibitors
  • Fusion Proteins, bcr-abl* / genetics
  • Fusion Proteins, bcr-abl* / metabolism
  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / drug therapy
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / enzymology
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / genetics
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / pathology
  • Leukocytes, Mononuclear / enzymology
  • Leukocytes, Mononuclear / pathology
  • Myeloid Progenitor Cells* / enzymology
  • Myeloid Progenitor Cells* / pathology
  • Neoplastic Stem Cells* / enzymology
  • Neoplastic Stem Cells* / pathology
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyrimidines / therapeutic use*

Substances

  • Protein Kinase Inhibitors
  • Pyrimidines
  • Fusion Proteins, bcr-abl
  • nilotinib
  • Dasatinib